Abdul-Majid Khairul Bariah, Wefer Judit, Stadelmann Christine, Stefferl Andreas, Lassmann Hans, Olsson Tomas, Harris Robert A
Neuroimmunology Unit, Karolinska Hospital, SE-171 76 Stockholm, Sweden.
J Neuroimmunol. 2003 Aug;141(1-2):10-9. doi: 10.1016/s0165-5728(03)00210-8.
Experimental autoimmune encephalomyelitis (EAE) was induced with myelin oligodendrocyte glycoprotein (MOG(1-125)) in CD4(-/-) and CD8(-/-) DBA/1 mice. Both gene-deleted mice developed clinical signs of EAE, albeit milder than in wild-type mice, suggesting that both CD4(+) and CD8(+) cells participate in disease development. Demyelination and inflammation in the central nervous system was reduced in the absence of CD8(+) T cells. Antibody depletion of CD4(+) cells completely protected CD8(-/-) mice from MOG-induced EAE while depletion of CD8(+) cells in CD4(-/-) mice resulted in fewer EAE incidence compared to that in control antibody-treated mice. Antibody depletion of CD4(+) cells in wild-type mice protected from EAE, but not depletion of CD8(+) cells, although demyelination was reduced on removal of CD8(+) T cells. Immunization with immunodominant MOG(79-96) peptide led to EAE only in the presence of pertussis toxin (PT) in the inoculum. PT also triggered an earlier onset and more severe EAE in CD8(-/-) mice. We interpret our findings such that in an ontogenic lack of CD4(+) T cells, EAE is mediated by CD8(+) and elevated levels of alphabetaCD4(-)CD8(-) cells, and that CNS damage is partly enacted by the activity of CD8(+) T cells.
用髓鞘少突胶质细胞糖蛋白（MOG(1-125)）在CD4(-/-)和CD8(-/-) DBA/1小鼠中诱导实验性自身免疫性脑脊髓炎（EAE）。两种基因敲除小鼠都出现了EAE的临床症状，尽管比野生型小鼠轻，这表明CD4(+)和CD8(+)细胞都参与了疾病的发展。在没有CD8(+) T细胞的情况下，中枢神经系统的脱髓鞘和炎症减轻。用抗体清除CD4(+)细胞可使CD8(-/-)小鼠完全免受MOG诱导的EAE影响，而在CD4(-/-)小鼠中清除CD8(+)细胞导致EAE发病率比对照抗体处理的小鼠低。在野生型小鼠中用抗体清除CD4(+)细胞可预防EAE，但清除CD8(+)细胞则不能，尽管去除CD8(+) T细胞后脱髓鞘有所减轻。用免疫显性MOG(79-96)肽免疫仅在接种物中存在百日咳毒素（PT）时才导致EAE。PT还引发CD8(-/-)小鼠中EAE更早发作且更严重。我们对研究结果的解释是，在个体发育中缺乏CD4(+) T细胞时，EAE由CD8(+)和αβCD4(-)CD8(-)细胞水平升高介导，并且中枢神经系统损伤部分由CD8(+) T细胞的活性引起。
